Transradial Access for High-Risk Percutaneous Coronary Intervention: Implications of the Risk-Treatment Paradox.

[Figure: see text].

Costs associated with transradial access and same-day discharge after percutaneous coronary intervention: a systematic review and meta-analysis.

Transradial access for PCI (TRI) along with same day discharge (SDD) is associated with varying estimates of cost savings depending on the population studied, the clinical scenario and application to low-risk vs high-risk patients. A summary estimate of the true cost savings of TRI and SDD are unknown. We searched the PubMed, EMBASE®, CINAHL® and Google Scholar® databases for published studies on hospitalization costs of TRI and SDD. Primary outcome of interest in all included studies was the cost saving with TRI (or SDD), inflation-corrected US$ 2018 values using the medical consumer price index. For meta-analytic synthesis, we used Hedges' summary estimate (g) in a random-effects framework of the DerSimonian and Laird model, with inverse variance weights. Heterogeneity was quantified using the I2 statistic. The cost savings of TRI from four US studies of 349,757 patients reported a consistent and significant cost saving associated with TRI after accounting for currency inflation, of US$ 992 (95% CI US$ 850-1,134). The cost savings of SDD from six US studies of 1,281,228 patients, after inflation-correcting to the year 2018, were US$ 3,567.58 (95% CI US$ 2,303-4,832). In conclusion, this meta-analysis demonstrates that TRI and SDD are associated with mean cost reductions of by approximately US$ 1,000/patient and US$ 3,600/patient, respectively, albeit with wide heterogeneity in the cost estimates. When combined with the safety of TRI and SDD, this meta-analysis underscores the value of combining TRI and SDD pathways and calls for a wide-ranging practice change in the direction of TRI and SDD.

Artificial neural network-based prediction of prolonged length of stay and need for post-acute care in acute coronary syndrome patients undergoing percutaneous coronary intervention.

BACKGROUND: Prolonged length of stay (LOS) and post-acute care after percutaneous coronary intervention (PCI) is common and costly. Risk models for predicting prolonged LOS and post-acute care have limited accuracy. Our goal was to develop and validate models using artificial neural networks (ANN) to predict prolonged LOS > 7days and need for post-acute care after PCI. METHODS: We defined prolonged LOS as ≥7 days and post-acute care as patients discharged to: extended care, transitional care unit, rehabilitation, other acute care hospital, nursing home or hospice care. Data from 22 675 patients who presented with ACS and underwent PCI was shuffled and split into a derivation set (75% of dataset) and a validation dataset (25% of dataset). Calibration plots were used to examine the overall predictive performance of the MLP by plotting observed and expected risk deciles and fitting a lowess smoother to the data. Classification accuracy was assessed by a receiver-operating characteristic (ROC) and area under the ROC curve (AUC). RESULTS: Our MLP-based model predicted prolonged LOS with an accuracy of 90.87% and 88.36% in training and test sets, respectively. The post-acute care model had an accuracy of 90.22% and 86.31% in training and test sets, respectively. This accuracy was achieved with quick convergence. Predicted probabilities from the MLP models showed good (prolonged LOS) to excellent calibration (post-acute care). CONCLUSIONS: Our ANN-based models accurately predicted LOS and need for post-acute care. Larger studies for replicability and longitudinal studies for evidence of impact are needed to establish these models in current PCI practice.

Sociodemographic differences in utilization and outcomes for temporary cardiovascular mechanical support in the setting of cardiogenic shock.

BACKGROUND: Temporary mechanical circulatory support (MCS) devices are increasingly used in cardiogenic shock, but whether sociodemographic differences by sex, race and/or ethnicity, insurance status, and neighborhood poverty exist in the utilization of these devices is unknown. METHODS: Retrospective cross-sectional study using the National Inpatient Sample for 2012-2017. Logistic regression models were used to examine predictors of use of temporary MCS devices and for in-hospital mortality, clustering by hospital-year. RESULTS: Our study population included 109,327 admissions for cardiogenic shock. Overall, 14.3% of admissions received an intra-aortic balloon pump, 4.2% a percutaneous ventricular assist device, and 1.8% extracorporeal membranous oxygenation (ECMO). After adjusting for age, comorbidities, and hospital characteristics, use of temporary MCS was lower in women compared to men (adjusted odds ratio [aOR] = 0.76, P < .001), Black patients compared to white ones (aOR = 0.73, P < .001), those insured by Medicare (aOR = 0.75, P < .001), Medicaid (aOR = 0.74, P < .001), or uninsured (aOR = 0.90, P = .015) compared to privately insured, and those in the lowest income neighborhoods (aOR = 0.94, P = .003) versus other neighborhoods. Women, admissions covered by Medicare, Medicaid, or uninsured, and those from low-income neighborhoods also had higher mortality rates even after adjustment for MCS implantation. CONCLUSIONS: There are differences in the use of temporary MCS in the setting of cardiogenic shock among specific populations within the United States. The growing use of MCS for treating cardiogenic shock highlights the need to better understand its impact on outcomes.

Synthesis of systematic reviews of percutaneous device closure of patent foramen ovale (PFO) for prevention of recurrent cryptogenic stroke: Redundant publications and methodological deficiencies.

Critical assessments of systemic reviews and meta-analyses have found them to often be redundant, lacking in novel perspectives, of poor methodological quality, and written by authors with potential conflicts of interest. We sought to investigate these issues as they relate to systemic reviews and meta-analyses of percutaneous patent foramen ovale closure for the prevention of recurrent cryptogenic stroke.

Clinical and Echocardiographic Features Associated With Improved Survival in Patients With Severe Aortic Stenosis Undergoing Balloon Aortic Valvuloplasty (BAV).

BACKGROUND: Balloon aortic valvuloplasty (BAV) is used in high-risk patients with severe aortic stenosis (AS) when the benefit of transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) is unclear. Our objective was to identify clinical or echocardiographic features that identify patients likely to benefit from BAV. METHODS: We studied 141 consecutive patients who underwent BAV from July, 2011 to October, 2017. Clinical characteristics, routine echocardiographic parameters, and speckle tracking imaging of global longitudinal strain (GLS) were assessed before and after BAV. The primary outcome was all-cause mortality as ascertained by the National Death Index. RESULTS: There were 141 patients, median age, 80 years (interquartile range [IQR], 74-87 years) with severe AS (median aortic valve area, 0.66 cm²; IQR, 0.53-0.79 cm²) and median mean gradient of 36 mm Hg (IQR, 27-48 mm Hg) who underwent BAV. The 1-year mortality rate was 52%. Characteristics associated with survival were New York Heart Association class I symptoms, lower brain natriuretic peptide level, higher left ventricular ejection fraction (LVEF) >53%, and higher GLS (>13.2%; absolute values were used for GLS). Landmark analysis at 60 days showed the 47 patients who underwent TAVR/SAVR after BAV had significantly better 1-year survival than those who did not (P<.001). CONCLUSION: A high 1-year mortality rate was observed in severe AS patients selected for BAV. LVEF and left ventricular (LV)-GLS offer similar prognostic value for 1-year mortality; however, LV-GLS may have potentially increased clinical utility, as it provides a clear threshold for predicting poor outcomes compared with LVEF. As patients who undergo TAVR/SAVR have markedly improved mortality, careful consideration should be given to advance definitive valve therapy in carefully selected BAV patients.

Glucose 6-Phosphate Accumulates via Phosphoglucose Isomerase Inhibition in Heart Muscle.

RATIONALE: Metabolic and structural remodeling is a hallmark of heart failure. This remodeling involves activation of the mTOR (mammalian target of rapamycin) signaling pathway, but little is known on how intermediary metabolites are integrated as metabolic signals. OBJECTIVE: We investigated the metabolic control of cardiac glycolysis and explored the potential of glucose 6-phosphate (G6P) to regulate glycolytic flux and mTOR activation. METHODS AND RESULTS: We developed a kinetic model of cardiomyocyte carbohydrate metabolism, CardioGlyco, to study the metabolic control of myocardial glycolysis and G6P levels. Metabolic control analysis revealed that G6P concentration is dependent on phosphoglucose isomerase (PGI) activity. Next, we integrated ex vivo tracer studies with mathematical simulations to test how changes in glucose supply and glycolytic flux affect mTOR activation. Nutrient deprivation promoted a tight coupling between glucose uptake and oxidation, G6P reduction, and increased protein-protein interaction between hexokinase II and mTOR. We validated the in silico modeling in cultured adult mouse ventricular cardiomyocytes by modulating PGI activity using erythrose 4-phosphate. Inhibition of glycolytic flux at the level of PGI caused G6P accumulation, which correlated with increased mTOR activation. Using click chemistry, we labeled newly synthesized proteins and confirmed that inhibition of PGI increases protein synthesis. CONCLUSIONS: The reduction of PGI activity directly affects myocyte growth by regulating mTOR activation.

The cardiac arrest survival score: A predictive algorithm for in-hospital mortality after out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality. Current methods for predicting mortality post-arrest require data unavailable at the time of initial medical contact. We created and validated a risk prediction model for patients experiencing OHCA who achieved return of spontaneous circulation (ROSC) which relies only on objective information routinely obtained at first medical contact. METHODS: We performed a retrospective evaluation of 14,892 OHCA patients in a large metropolitan cardiac arrest registry, of which 3952 patients had usable data. This population was divided into a derivation cohort (n = 2,635) and a verification cohort (n = 1,317) in a 2:1 ratio. Backward stepwise logistic regression was used to identify baseline factors independently associated with death after sustained ROSC in the derivation cohort. The cardiac arrest survival score (CASS) was created from the model and its association with in-hospital mortality was examined in both the derivation and verification cohorts. RESULTS: Baseline characteristics of the derivation and verification cohorts were not different. The final CASS model included age >75 years (odds ratio [OR] = 1.61, confidence interval [CI][1.30-1.99], p < 0.001), unwitnessed arrest (OR = 1.95, CI[1.58-2.40], p < 0.001), home arrest (OR = 1.28, CI[1.07-1.53], p = 0.008), absence of bystander CPR (OR = 1.35, CI[1.12-1.64], p = 0.003), and non-shockable initial rhythm (OR = 3.81, CI[3.19-4.56], p < 0.001). The area under the curve for the model derivation and model verification cohorts were 0.7172 and 0.7081, respectively. CONCLUSION: CASS accurately predicts mortality in OHCA patients. The model uses only binary, objective clinical data routinely obtained at first medical contact. Early risk stratification may allow identification of more patients in whom timely and aggressive invasive management may improve outcomes.

The Incidence and Outcome Differences in Severe Sepsis with and without Lactic Acidosis.

INTRODUCTION: To compare the incidence, characteristics, and outcomes of lactate expressors and nonexpressors in patients with severe sepsis and septic shock. METHODS: This is a retrospective cohort study of patients with severe sepsis and septic shock who presented over a 40-month period to an academic tertiary care center. Primary outcome of interest was in-hospital mortality. Secondary outcomes were hospital length of stay (LOS), Intensive Care Unit (ICU) LOS, and escalation of care. RESULTS: Three hundred and thirty-eight patients met inclusion criteria and were divided into a lactate expressor group (n = 197; initial lactate ≥2.5 mmol/L) and a nonexpressor group (n = 141; lactate <2.5 mmol/L). The mortality rate was 46.2% for lactate expressors and 24.8% for nonexpressors. There were no significant differences in hospital or ICU LOS. The escalation-of-care rate in the severe sepsis nonexpressor group was more than double that found in the expressor group: 16.5% versus 6.2% (P = 0.040). The two groups had baseline differences: expressor group had a higher median Acute Physiology and Chronic Health Evaluation II (APACHE II) illness severity score, and nonexpressors had an increased prevalence of comorbid conditions. APACHE II score (odds ratio [OR] 1.10 (1.07-1.14), P < 0.001) and being in the expressor group (OR 1.72 [1.03-2.89], P = 0.039) increased the odds of mortality. CONCLUSIONS: In patients with severe sepsis and septic shock, lactate nonexpressors are common. Although the mortality in this cohort is less than its counterparts who present with lactate elevation, it is still significant which warrants vigilance in their care.

Outcomes of severe sepsis and septic shock patients after stratification by initial lactate value.

BACKGROUND: In the setting of severe sepsis and septic shock, mortality increases when lactate levels are ≥ 4 mmol/L. However, the consequences of lower lactate levels in this population are not well understood. The study aimed to determine the in-hospital mortality associated with severe sepsis and septic shock when initial lactate levels are < 4 mmol/L. METHODS: This is a retrospective cohort study of septic patients admitted over a 40-month period. Totally 338 patients were divided into three groups based on initial lactate values. Group 1 had lactate levels < 2 mmol/L; group 2: 2-4 mmol/L; and group 3: ≥ 4 mmol/L. The primary outcome was in-hospital mortality. RESULTS: There were 111 patients in group 1, 96 patients in group 2, and 131 in group 3. The mortality rates were 21.6%, 35.4%, and 51.9% respectively. Univariate analysis revealed the mortality differences to be statistically significant. Multivariate logistic regression demonstrated higher odds of death with higher lactate tier group, however the findings did not reach statistical significance. CONCLUSION: This study found that only assignment to group 3, initial lactic acid level of ≥ 4 mmol/L, was independently associated with increased mortality after correcting for underlying severity of illness and organ dysfunction. However, rising lactate levels in the other two groups were associated with increased severity of illness and were inversely proportional to prognosis.

Outcomes of severe sepsis and septic shock patients after stratification by initial lactate value / 世界急诊医学杂志（英文）

BACKGROUND: In the setting of severe sepsis and septic shock, mortality increases when lactate levels are ≥ 4 mmol/L. However, the consequences of lower lactate levels in this population are not wel understood. The study aimed to determine the in-hospital mortality associated with severe sepsis and septic shock when initial lactate levels are < 4 mmol/L. METHODS: This is a retrospective cohort study of septic patients admitted over a 40-month period. Totally 338 patients were divided into three groups based on initial lactate values. Group 1 had lactate levels < 2 mmol/L; group 2: 2–4 mmol/L; and group 3: ≥ 4 mmol/L. The primary outcome was in-hospital mortality. RESULTS: There were 111 patients in group 1, 96 patients in group 2, and 131 in group 3. The mortality rates were 21.6％, 35.4％, and 51.9％ respectively. Univariate analysis revealed the mortality differences to be statistically significant. Multivariate logistic regression demonstrated higher odds of death with higher lactate tier group, however the findings did not reach statistical significance. CONCLUSION: This study found that only assignment to group 3, initial lactic acid level of ≥ 4 mmol/L, was independently associated with increased mortality after correcting for underlying severity of illness and organ dysfunction. However, rising lactate levels in the other two groups were associated with increased severity of illness and were inversely proportional to prognosis.

Coordination of Cellular Localization-Dependent Effects of Sumoylation in Regulating Cardiovascular and Neurological Diseases.

Sumoylation, a reversible post-transcriptional modification process, of proteins are involved in cellular differentiation, growth, and even motility by regulating various protein functions. Sumoylation is not limited to cytosolic proteins as recent evidence shows that nuclear proteins, those associated with membranes, and mitochondrial proteins are also sumoylated. Moreover, it is now known that sumoylation plays an important role in the process of major human ailments such as malignant, cardiovascular and neurological diseases. In this chapter, we will highlight and discuss how the localization of SUMO protease and SUMO E3 ligase in different compartments within a cell regulates biological processes that depend on sumoylation. First, we will discuss the key role of sumoylation in the nucleus, which leads to the development of endothelial dysfunction and atherosclerosis . We will then discuss how sumoylation of plasma membrane potassium channel proteins are involved in epilepsy and arrhythmia. Mitochondrial proteins are known to be also sumoylated, and the importance of dynamic-related protein 1 (DRP1) sumoylation on mitochondrial function will be discussed. As we will emphasize throughout this review, sumoylation plays crucial roles in different cellular compartments, which is coordinately regulated by the translocation of various SUMO proteases and SUMO E3 ligase. Comprehensive approach will be necessary to understand the molecular mechanism for efficiently moving around various enzymes that regulate sumoylation within cells.

Ewing Sarcoma in the Right Ventricle.

Ewing sarcoma is the second most prevalent malignant primary bone tumor but constitutes only a small proportion of cardiac metastases. We present a case of asymptomatic Ewing sarcoma metastatic to the right ventricle. A 36-year-old man presented for evaluation and resection of a pedunculated right ventricular cardiac tumor. Three years before, he had been diagnosed with translocation-negative Ewing sarcoma, for which he had undergone chemotherapy and amputation of the left leg below the knee. We resected the right ventricular tumor. Analysis of the resected mass supported the diagnosis of metastatic Ewing sarcoma. Postoperative transthoracic echocardiograms showed normal biventricular size and function. One year later, the patient had no recurrence of the sarcoma. In addition to discussing this case, we review the relevant medical literature.

Primary Cardiac Sarcoidosis with Syncope and Refractory Atrial Arrhythmia: A Case Report and Review of the Literature.

We discuss the case of a 38-year-old black man who presented at our hospital with his first episode of syncope, recently developed atrial arrhythmias refractory to pharmacologic therapy, and a left atrial thrombus. He was diagnosed with primary cardiac sarcoidosis characterized by predominant involvement of the epicardium that caused atrial fibrillation and atrial flutter. Histologic analysis of his epicardial lesions yielded a diagnosis of sarcoidosis. This patient's atrial arrhythmia was successfully treated with a hybrid operation that involved resection of his atrial appendage, an Epicor maze procedure, and radiofrequency ablation during a catheter-based electrophysiologic study. The cardiac sarcoidosis was successfully managed with corticosteroid therapy. Our case report shows that sarcoidosis can initially manifest itself as syncope with new-onset atrial arrhythmia. Sarcoidosis is important in the differential diagnosis because of its progressive nature and its potential for treatment with pharmacologic, surgical, and catheter-based interventions.

Effect of Therapeutic Hypothermia on Survival to Hospital Discharge in Out-of-hospital Cardiac Arrest Secondary to Nonshockable Rhythms.

OBJECTIVES: Therapeutic hypothermia has been shown to improve neurologic outcome and survival in out-of-hospital cardiac arrest (OHCA) following return of spontaneous circulation (ROSC), and current guidelines recommend therapeutic hypothermia for all comatose survivors of OHCA. However, recommendations for nonshockable rhythms are not as strongly supported. Our study aims to provide further evidence on the use of therapeutic hypothermia in nonshockable rhythms. METHODS: A multivariate analysis with propensity score matching was performed using a cardiac arrest registry maintained by the Houston Fire Department. The analysis was limited to adult patients achieving ROSC following OHCA secondary to nonshockable rhythm in Houston from 2007 to 2012 with definitive information regarding the implementation of therapeutic hypothermia. The primary outcome was survival to hospital discharge. RESULTS: Of 9,479 records identified for analysis, 7,839 had an initial nonshockable rhythm. Of these, 2,609 (33.3%) had sustained ROSC and 1,768 (22.6%) were admitted to the hospital. Data on therapeutic hypothermia use were available for 696 patients, with 335 (48.1%) receiving therapeutic hypothermia. Propensity score matching yielded 260 case/control pairs. The odds of survival to hospital discharge was an odds ratio of 1.07 (95% confidence interval = 0.71 to 1.60) for those in the therapeutic hypothermia group versus the nontherapeutic hypothermia group (p = 0.79). CONCLUSIONS: Based on this retrospective study, therapeutic hypothermia is not associated with improved survival in patients with OHCA secondary to nonshockable rhythms. Given the limitations of our study, further prospective trials to assess the effect of therapeutic hypothermia for OHCA with nonshockable rhythms are warranted.